Up to now, about half of drug molecules are present in the form of salts and are administrated in the form of salts. By forming salts, physical and chemical properties of drugs can be improved, such as solubility, dissolution rate, bioavailability, hygroscopicity, flowability, bulk density, stability, melting point, milling property, convenience for preparation and purification, or the like. If the same drug has different crystal forms, the bioavailability of different crystal forms will be different. Moreover, the stability, flowability and compressibility of different crystal forms will be different. Thus, such different physical and chemical properties will influence use of the drug to some extent.
6-halo-3-butyl-1(3H)-isobenzofuranone compound has certain therapeutic effect on ischemic cerebrovascular disease, and can promote recovery of impaired neural function in patients. 6-halo-3-butyl-1(3H)-isobenzofuranone is substantially insoluble in water, thus it is generally prepared as halo-2-(α-hydroxypentyl)benzoic acid, so as to improve the solubility. However, halo-2-(α-hydroxypentyl)benzoic acid is very unstable under room temperature and is easy to convert to 6-halo-3-butyl-1(3H)-isobenzofuranone, therefore this is disadvantageous for administration. It can be stored at low temperature (4° C.) for limited storage period.
Chinese patent No. 01109795.7 discloses salts of 2-(α-hydroxypentyl)benzoic acid and the preparation method and use thereof in the first time, which relates to salts of monovalent metal ions, divalent metal ions and organic bases. It specifically discloses the salts of potassium, sodium, calcium, magnesium, zinc, aniline, benzylamine, morpholine, and diethylamine. Its specification also discloses effect of the potassium salt on brain infarction area in rats with local brain ischemia, effect of the potassium salt on platelet aggregation in rats, and protective effect of the potassium salt on ischemia of isolated heart and arrhythmias following reperfusion in rats, thereby indicating the potassium salt produces beneficial effect in said experiments. Chinese patent No. 200410048268.9 and Chinese patent No. 200610073077.7 respectively disclose the preparations and activity tests of the corresponding chiral salts of 2-(α-hydroxypentyl)benzoic acid. Chinese patent No. 200710054215.1 discloses the synthesis and activity test of the halogenated compound 6-halo-3-butyl-1(3H)-isobenzofuranone in the first time, wherein the halogenated compound 6-halo-3-butyl-1(3H)-isobenzofuranone has obviously better activity than butylphthalide. Chinese patent No. 200810230890. X discloses the preparation method of halogenated 2-(α-hydroxypentyl)benzoic acid salts compounds and pharmaceutical use thereof in the first time, which relates to salts of monovalent metal ions, divalent metal ions and organic bases. It specifically discloses the salts of sodium, potassium, calcium, and benzylamine. Its specification also discloses the activity of the halogenated 2-(α-hydroxypentyl)benzoic acid potassium salt for prevention and treatment of heart and brain ischemic diseases, for improving heart and brain circulatory disorders and antithrombotic effect, and the like, wherein activity of the halogenated 2-(α-hydroxypentyl)benzoic acid potassium salt is better than butylphthalide, 6-halo-3-butyl-1(3H)-isobenzofuranone, and 2-(α-hydroxypentyl)benzoic acid salt. However, the above patents do not relate to research of crystal forms of 5-halo-2-(α-hydroxypentyl)benzoic acid salts. Therefore, it is of practical importance to study different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt and to improve pharmaceutical stability and water-solubility of said compound, thereby meeting the requirements for administration. In the meantime, the different crystal forms of 5-bromo-2-(α-hydroxypentyl)benzoic acid sodium salt produce obviously better therapeutic effect than 5-bromo-2-(α-hydroxypentyl)benzoic acid potassium salt (CN ZL200810230890.X). Said better therapeutic effect has not been reported by any literatures in the art until now.